{"title":"通过血清代谢组学技术筛选顺铂诱发大鼠急性肾损伤的早期生物标志物","authors":"Jinru Yang, Mingkang Zhang, Fenglin Ran, Xueyan Gou, Yanrong Ma, Xinan Wu","doi":"10.29271/jcpsp.2024.08.936","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To systematically identify early biomarkers of cisplatin-induced acute kidney injury (AKI) in rats.</p><p><strong>Study design: </strong>An experimental study. Place and Duration of the Study: Experimental Animal Laboratory of Lanzhou University, Gansu, China, and the Department of Pharmacy, The First Hospital of Lanzhou University, Gansu, China, from July 2022 to October 2023.</p><p><strong>Methodology: </strong>In this study, an AKI model was established by continuously injecting cisplatin into rats at a dose of 1 mg/kg once a day for control group and for 2, 3, 4, and 5 days to other four groups, respectively. Subsequently, rat plasma samples were collected for metabolomics analysis to identify early differentiated metabolites in the plasma prior to creatinine elevation. Furthermore, accurate HPLC-MS/MS methods were developed to validate the biomarker variation in other AKI models.</p><p><strong>Results: </strong>The occurrence of time-dependent renal cortical injury and significant alterations of creatinine (Cr) concentration were observed on day-4 and 5, which demonstrated successful model construction. Sixty-six compounds changed on Day-2 while 61 compounds changed on Day-3. Eleven compounds with variable importance in projection (VIP) >1.5 and false discover rate (FDR) <0.2 were selected and identified by HPLC-MS/MS. Among these, N-acetylglutamine and citramalic acid changed earlier than serum creatinine (sCr) in the AKI model.</p><p><strong>Conclusion: </strong>N-acetylglutamine and citramalic acid may serve as early biomarker of cisplatin-induced AKI.</p><p><strong>Key words: </strong>Acute kidney injury, Biomarker, Cisplatin, Metabolomics, LC-MS/MS, Rats.</p>","PeriodicalId":94116,"journal":{"name":"Journal of the College of Physicians and Surgeons--Pakistan : JCPSP","volume":"34 8","pages":"936-941"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Screening for Early Biomarkers of Cisplatin-Induced Acute Kidney Injury in Rats Through Serum Metabolomics Technology.\",\"authors\":\"Jinru Yang, Mingkang Zhang, Fenglin Ran, Xueyan Gou, Yanrong Ma, Xinan Wu\",\"doi\":\"10.29271/jcpsp.2024.08.936\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To systematically identify early biomarkers of cisplatin-induced acute kidney injury (AKI) in rats.</p><p><strong>Study design: </strong>An experimental study. Place and Duration of the Study: Experimental Animal Laboratory of Lanzhou University, Gansu, China, and the Department of Pharmacy, The First Hospital of Lanzhou University, Gansu, China, from July 2022 to October 2023.</p><p><strong>Methodology: </strong>In this study, an AKI model was established by continuously injecting cisplatin into rats at a dose of 1 mg/kg once a day for control group and for 2, 3, 4, and 5 days to other four groups, respectively. Subsequently, rat plasma samples were collected for metabolomics analysis to identify early differentiated metabolites in the plasma prior to creatinine elevation. Furthermore, accurate HPLC-MS/MS methods were developed to validate the biomarker variation in other AKI models.</p><p><strong>Results: </strong>The occurrence of time-dependent renal cortical injury and significant alterations of creatinine (Cr) concentration were observed on day-4 and 5, which demonstrated successful model construction. Sixty-six compounds changed on Day-2 while 61 compounds changed on Day-3. Eleven compounds with variable importance in projection (VIP) >1.5 and false discover rate (FDR) <0.2 were selected and identified by HPLC-MS/MS. Among these, N-acetylglutamine and citramalic acid changed earlier than serum creatinine (sCr) in the AKI model.</p><p><strong>Conclusion: </strong>N-acetylglutamine and citramalic acid may serve as early biomarker of cisplatin-induced AKI.</p><p><strong>Key words: </strong>Acute kidney injury, Biomarker, Cisplatin, Metabolomics, LC-MS/MS, Rats.</p>\",\"PeriodicalId\":94116,\"journal\":{\"name\":\"Journal of the College of Physicians and Surgeons--Pakistan : JCPSP\",\"volume\":\"34 8\",\"pages\":\"936-941\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the College of Physicians and Surgeons--Pakistan : JCPSP\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.29271/jcpsp.2024.08.936\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the College of Physicians and Surgeons--Pakistan : JCPSP","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.29271/jcpsp.2024.08.936","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Screening for Early Biomarkers of Cisplatin-Induced Acute Kidney Injury in Rats Through Serum Metabolomics Technology.
Objective: To systematically identify early biomarkers of cisplatin-induced acute kidney injury (AKI) in rats.
Study design: An experimental study. Place and Duration of the Study: Experimental Animal Laboratory of Lanzhou University, Gansu, China, and the Department of Pharmacy, The First Hospital of Lanzhou University, Gansu, China, from July 2022 to October 2023.
Methodology: In this study, an AKI model was established by continuously injecting cisplatin into rats at a dose of 1 mg/kg once a day for control group and for 2, 3, 4, and 5 days to other four groups, respectively. Subsequently, rat plasma samples were collected for metabolomics analysis to identify early differentiated metabolites in the plasma prior to creatinine elevation. Furthermore, accurate HPLC-MS/MS methods were developed to validate the biomarker variation in other AKI models.
Results: The occurrence of time-dependent renal cortical injury and significant alterations of creatinine (Cr) concentration were observed on day-4 and 5, which demonstrated successful model construction. Sixty-six compounds changed on Day-2 while 61 compounds changed on Day-3. Eleven compounds with variable importance in projection (VIP) >1.5 and false discover rate (FDR) <0.2 were selected and identified by HPLC-MS/MS. Among these, N-acetylglutamine and citramalic acid changed earlier than serum creatinine (sCr) in the AKI model.
Conclusion: N-acetylglutamine and citramalic acid may serve as early biomarker of cisplatin-induced AKI.
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